INHIBITION OF HIV INTEGRASE BY DNA INTERCALATORS (MEETING ABSTRACT)

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

INHIBITION OF HIV INTEGRASE BY DNA INTERCALATORS (MEETING ABSTRACT)

Proc Annu Meet Am Assoc Cancer Res; 33:A2177 1992. Unique Identifier : AIDSLINE ICDB/92684723
Fesen MR; Leteurtre F; Kohn KW; Pommier Y; Lab. of Molecular Pharmacology, DCT, NCI, Bethesda, MD 20892

Abstract: Integration of HIV DNA into the host genome after viral DNA synthesis by reverse transcriptase represents an essential step in the HIV life cycle. Because of general similarity in the action of HIV integrase (In) to topoisomerases, various inhibitors were tested against In. A 21-mer duplex oligonucleotide corresponding to the U5 end of HIV DNA end-labeled with 32P was used to test for In cleavage and integration activities (Craigie et al, Nucleic Acids Res 19:2729, 1991). Inactive drugs included camptothecin, etoposides, distamycin, oxathiin carboxanilide (Uniroyal Jr), dinucleotides, merbarone and ICRF 159 and 187. Active agents, all intercalators, included doxorubicin greater than ditercalinium greater than ellipticine greater than ethidium. Hydroxyrubicin and 9-aminoacridine were weakly active. While In inhibition is limited to those topoisomerase II inhibitors which are DNA intercalators, this inhibition does not closely correlate with DNA binding affinity, as doxorubicin and ditercalinium were equally active, while ditercalinium has a much greater DNA binding affinity. In conclusion, doxorubicin and other DNA intercalators are active against HIV integrase.

Keywords: Camptothecin/PHARMACOLOGY Distamycins/PHARMACOLOGY DNA Nucleotidyltransferases/*ANTAGONISTS & INHIB DNA, Viral/*DRUG EFFECTS Etoposide/PHARMACOLOGY Intercalating Agents/*PHARMACOLOGY Nucleic Acid Heteroduplexes Nucleotides/PHARMACOLOGY Oxathiins/PHARMACOLOGY Razoxane/PHARMACOLOGY Thiobarbiturates/PHARMACOLOGY ABSTRACT
921030
M92A1034

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